Advanced Radiation Techniques Reduce Side Effects in Head and Neck Cancer Treatment

ScienceDaily (May 17, 2010) — Researchers at the University of Michigan Comprehensive Cancer Center have applied advanced radiation techniques for head and neck cancer to avoid treating critical structures that affect swallowing and eating. A new study shows these principles and techniques treated the cancer effectively while greatly reducing long-term swallowing complications.

The researchers applied highly conformal, intensity-modulated radiation therapy and knowledge of the anatomy and physiology of the structures involved to carefully craft a novel treatment plan that avoids certain muscles in the mouth and throat that are most involved in swallowing. Generally, head and neck tumors do not spread to these structures.

Of the 73 patients treated with this technique, all but four were eating a normal diet after their treatment ended and only one was dependent on a feeding tube. Typically up to 20 percent of head and neck cancer patients remain dependent on a feeding tube after finishing an intensive course of radiation treatment concurrent with chemotherapy.

Results of the study appear online in the Journal of Clinical Oncology.

"More aggressive treatments for head and neck cancer have improved cancer control, but at the expense of quality of life. In this study, we did not compromise tumor control and we were able to improve this important quality of life measure," says study author Avraham Eisbruch, M.D., professor of radiation oncology at the U-M Medical School.

Scar tissue from radiation treatments to the head and neck often creates long-term problems with swallowing and eating solid foods that do not improve over time. In this study, 29 percent of the patients required a temporary feeding tube during treatment because of pain while swallowing. But by one year after treatment, only one of the 73 patients on the study still required a feeding tube. Questionnaires to assess eating and swallowing function showed that on average, patients had only slight difficulties up to two years after treatment.

No patients had a spread of their cancer to the untreated structures and few cancers recurred overall, suggesting it was not harmful to avoid treating these areas. After three years, 88 percent of patients were cancer-free.

Eisbruch and his colleagues were also leaders in pioneering head and neck radiation treatments that avoid the salivary glands, reducing significantly the severity of permanently dry mouth, which has previously been a major complication of radiotherapy for head and neck cancer.

"We seek a cure for these patients, but we also seek quality of life. As cure rates have improved in recent years, quality of life issues become more and more important. Our next steps are to identify which patients are likely to do well with treatment and reduce the intensity of treatment to limit the burden of these side effects," Eisbruch says.

The study looked at 73 patients with stage III or stage IV oropharyngeal cancer, including cancer of the tonsils or the base of the tongue. Patients were treated with seven weeks of daily intensity-modulated radiation therapy to the neck, designed to avoid the swallowing structures. Chemotherapy was administered weekly during this time. Patients were assessed with videofluoroscopy, an imaging procedure, periodically during treatment and up to two years after to assess swallowing. Swallowing was also assessed by doctors and through patient report using standard questionnaires.

Head and neck cancer statistics: 35,720 Americans will be diagnosed with head and neck cancer this year and 7,600 will die from the disease, according to the American Cancer Society

Not only does hypofractionated stereotactic radiotherapy (H-SRT) provide longer survival, patients do not experience side effects commonly seen with use of chemotherapies and targeted therapies, the researchers found. They believe these findings, reported online in the Journal of Clinical Oncology, set a new bar for the treatment of recurrent gliomas.

"In many centers, patients with tumor progression within six months after the initial conformal radiotherapy are denied a second radiotherapy course (such as H-SRT), based on the assumption that their prognosis is poor." said senior author Maria Werner-Wasik, M.D., professor of Radiation Oncology at Jefferson Medical College of Thomas Jefferson University and Co-Director of the Stereotactic Radiosurgery Program at Jefferson Hospital for Neuroscience. "Our findings support the recommendation that essentially all patients with progressive high-grade gliomas, who are in good shape and have tumors amenable to local radiotherapy, should be considered for H-SRT."

In this study of 147 patients -- currently the largest published series examining re-irradiation of recurrent high grade gliomas using H-SRT -- the median survival was about 11 months when H-SRT was used after cancer progressed. In comparison, the newest targeted therapy provides survival of about six months after cancer recurrence, the researchers said.

"These results are dramatic and we hope our experience influences how physicians treat patients with recurrent brain cancer," said study co-author David Andrews, M.D., professor of Neurological Surgery and Co-Director of the Stereotactic Radiosurgery Program. "We will need to design a randomized clinical trial to compare this method of treatment with current standard of care, and these data provide a compelling foundation for the design of such a trial."

The role of chemotherapy with radiation therapy has not been defined for recurrent gliomas and few studies have reported on this.

"While not a randomized trial, our study did not demonstrate a survival advantage in combining chemotherapy with H-SRT at recurrence compared to patients who received H-SRT alone," said the study's first author, Shannon Fogh, M.D., chief resident, Radiation Oncology at Thomas Jefferson University Hospital. "We feel it is important for clinicians to consider this before adding other therapy with associated toxicity and cost."

Thomas Jefferson University Hospital pioneered the use of this particular technology, which uses a stereotactic linear-accelerator-based radiosurgery unit that delivers tightly focused beams of radiation to tumor while sparing the surrounding normal tissue. It does this by using both magnetic resonance imaging (MRI) and computerized tomography (CT) images to create a three-dimensional representation of a tumor that is both anatomically and spatially exact. The radiation is then delivered in doses that conform precisely to the tumor. By irradiating just the tumor, and sparing normal tissue in the brain, physicians can use much higher doses over shorter periods of time.

"We can give a dose that is 50 percent beyond what has been considered the maximum dose of radiation the brain can tolerate," said Dr. Andrews. "We have learned over a 15 year experience that this dose is not only safe, but has almost doubled survival for these patients."

H-SRT can be delivered over two weeks, compared to five or six weeks for standard fractionation, researchers said.

"A shortened treatment course is not only more beneficial to patients with respect to quality of life and convenience but also may represent a significant decrease in cost associated with re-treatment," Dr. Fogh said.

In this study, the researchers determined that the patients who have the longest survival when treated with SRT after recurrence are those who are younger, have smaller tumors, and a shorter time between diagnosis and recurrence.

"Perhaps the most surprising and relevant finding from our review is a good prognosis in patients who recurred shortly after initial treatment," Dr. Fogh said. "Only two prior studies have examined prognosis in patients who recur shortly after treatment, and they showed conflicting results. It may be that the larger number of patients examined in our study, compared to the others, allowed us to more accurately assess this phenomenon."

ScienceDaily (Apr. 21, 2009) — Hypofractionated stereotactic radiotherapy was well-tolerated and improved symptoms in patients with recurrent low-grade glioma, according to researchers from the Kimmel Cancer Center at Jefferson. The data were presented at the AACR 100th Annual Meeting 2009.

In a subgroup of patients who also received chemotherapy with their hypofractionated sterotactic radiotherapy (H-SRT) the median survival time was more than three times longer than patients who only received H-SRT alone according to Shannon Fogh, M.D., a resident in Radiation Oncology at Thomas Jefferson University Hospital.

The study included 22 patients with evidence of glioma recurrence. All patients were given H-SRT as salvage therapy, and nine of the patients also received chemotherapy. The most common regimen was temozolomide (Temodar).

The median survival time from the time of H-SRT was nine months. Eleven of the patients had a response to treatment at six-week follow-up. In the subset of patients who received chemotherapy, the median survival time from time of H-SRT was 17 months vs. four months for patients who only received H-SRT.

The role of chemotherapy needs to be evaluated further, Dr. Fogh said, since the small number of patients in this study prevented a multivariate analysis that would account for age, performance status and tumor size.

"There really is no standard of care for recurrent gliomas," Dr. Fogh said. "H-SRT would be an attractive option because it allows a patient to have a shorter course of treatment. In our study, H-SRT was well-tolerated, and all patients were able to complete the full course of treatment."

ScienceDaily (May 5, 2009) — Vanderbilt-Ingram Cancer Center investigators have uncovered a mechanism that helps explain how lithium, a drug widely used to treat bipolar mood disorder, also protects the brain from damage that occurs during radiation treatments.

In the May 1 issue of the Journal of Clinical Investigation, Fen Xia, M.D., Ph.D., and colleagues show that lithium promotes DNA repair in healthy cells but not in brain tumor cells. The findings suggest that lithium treatment could offer a way to protect healthy brain tissue from damage that may occur during cranial radiation treatments.

Cranial irradiation is part of standard therapy for both primary and metastatic brain tumors. However, as with all treatment modalities, radiation often causes long-term side effects. In particular, neurological impairments – including lowered IQ, learning difficulties and memory loss – have been reported, especially in children treated for brain cancers. Radiation-induced damage to the healthy cells of the hippocampus, a brain structure crucial for learning and memory, is one likely source of these deficits.

These cognitive impairments have long-lasting effects on the quality of life for survivors, noted Xia, an assistant professor of Radiation Oncology and Cancer Biology.

"Because these patients can now survive longer and are being cured, alleviating long-term toxicity is becoming more important," she said.

Researchers have been searching for agents that could protect healthy brain tissue from radiation-induced damage. Previously, Vanderbilt-Ingram investigators – led by Dennis Hallahan, M.D., chair of Radiation Oncology and the Ingram Professor of Cancer Research – found that lithium treatment protects cultured hippocampal neurons from radiation-induced cell death and improves cognitive performance in irradiated mice.

But how lithium protects against radiation-induced damage is unclear.

Radiation kills tumor cells by damaging their DNA, but it can also attack the DNA of healthy cells. One of the most serious types of DNA damage is the chromosomal double-stranded break (DSB), in which both strands of the double helix are severed. Even a single unrepaired DSB can be lethal to a cell. Fortunately, the body has several different ways to repair DNA damage.

Working with Eddy Yang, M.D., Ph.D., a resident in the Radiation Oncology department and an American Board of Radiology Holman Research Scholar, and postdoctoral research fellow Hong Wang, M.D., Ph.D., Xia and colleagues examined DNA repair in lithium-treated mouse hippocampal neurons exposed to radiation.

They found that lithium did not prevent the generation of DSBs but promoted a particular kind of DNA repair – called nonhomologous end-joining (NHEJ) repair – which is the predominant repair mechanism used by normal neurons. Xia and colleagues showed biochemical and genetic evidence that radiation-induced DSBs were repaired with greater efficiency in lithium-treated cells via the NHEJ pathway.

However, none of these effects were observed in malignant glioma (brain tumor) cells, presumably because cancer cells generally utilize a different DNA repair mechanism, Xia said.

The researchers confirmed these findings in mice treated with cranial radiation. The results suggest that lithium protects healthy hippocampal neurons by promoting NHEJ-mediated DNA repair – but that lithium offers no protective effect in the brain tumor cells tested.

Since some tumors are resistant to radiation, Xia hopes that lithium treatment could provide a way to increase the radiation dose to levels that will kill the tumor cells while protecting healthy brain tissue. The team is launching an investigation of the safety and feasibility of lithium treatment in patients with low-grade glioma or brain metastases from small cell lung cancer.

"Right now, the problem is that we cannot kill the tumor completely because normal tissue toxicity limits the dose," Xia said. "So if we can protect normal tissue, we can hopefully give a higher dose to the tumor."

Researchers say a new technique for treating breast cancer means many women may eventually no longer need to undergo weeks of radiotherapy.

The international trial, published in the British medical journal The Lancet, suggests giving just one dose of radiation inside the breast during surgery is just as effective at preventing cancer recurring.

Breast cancer is responsible for 16 per cent of all female cancers worldwide and it is estimated that 500,000 women died from the disease in 2004.

Surgeon Mohammed Keshtgar from the Royal Free Hospital in London says he hopes the new treatment could be available within a couple of years.

"The early results indicate that it is safe and it is effective and I suspect within the next couple of years it should be available for every breast cancer patient," he said.

"In my view this is going to revolutionise the way we treat breast cancer."

Patients from Perth and Melbourne participated in the study.

The University of Western Australia's Professor Christobel Saunders says over 13,000 Australian women a year are diagnosed with breast cancer.

She says it offers another option for patients.

"Almost without exception, women have been delighted when they've just had to have the one-off treatment," she said.

"It's meant, particularly for ladies who live in the country, who have businesses or families, they've had to leave for many weeks to the city to have this treatment, if they only have to have it for one day it makes a huge difference for them."

Josephine Ford from London took part in the study and says the thought of five weeks of radiotherapy every day would be more daunting than anything else.

"The after-treatment is worse than the operation apparently," she said.

"I would shout it from the roof top - I feel fine. I've had mammograms since and an ultrasound - and there's nothing, it's all fine."

June 3, 2010 — Reradiating recurrent high-grade gliomas is a viable treatment strategy and could possibly be a standard salvage therapy in this setting, according to the authors of a new study.
Patients with recurrent high-grade gliomas who were treated with hypofractionated stereotactic radiation therapy (H-SRT) had survival rates that were comparable to the "best-reported results in the literature" for systemic agents, such as bevacizumab, according to the authors, led by Shannon Fogh, MD, from Thomas Jefferson University in Philadelphia, Pennsylvania.

In this study of 147 recurrent patients treated with H-SRT (median dose, 35.0 Gy in 3.5 Gy fractions), there was a median survival time of 11 months after the salvage H-SRT therapy, the authors report in their study, published online May 17 in the Journal of Clinical Oncology.

H-SRT also had "an improved toxicity profile and decreased cost," compared with systemic maintenance therapy with bevacizumab, which is approved by the US Food and Drug Administration for the treatment of recurrent glioblastomas, Dr. Fogh and coauthors point out.

They emphasize that their study was observational and that any comparisons between H-SRT and other therapies were based on published literature.

Nevertheless, the survival, toxicity, and cost data led the authors to conclude that H-SRT should be evaluated in future studies as the "standard salvage therapy for previously irradiated high-grade gliomas."

"In the eyes of many patients, neuro-oncologists, and even radiation oncologists who do not treat a large volume of brain patients, the concept of brain re-irradiation, particularly with such large doses given to the area previously treated with radiation therapy, seems dangerous and prohibitive," she told Medscape Oncology.

However, this study, which is the largest series to date on this approach, might change a few minds, suggest the authors.

No standard of care exists in this setting, said Dr. Fogh, but bevacizumab is "commonly given."

"It is important to realize, however, that the population treated with bevacizumab and H-SRT is not always the same; larger and more infiltrative tumors are more likely to get the drug, and those more compact and less infiltrative, the H-SRT. Those 2 approaches to salvage can be looked at as complementary, at least in a proportion of patients," she explained.

Study Rationale and Design

H-SRT seems like a good approach in patients with recurrent gliomas because of "their grim prognosis," say the study authors.

"It is imperative to consider quality of life when evaluating treatment options," they note. Thus, the shorter treatment schedule with hypofractionation (2 weeks vs 3 or 4 weeks) is a plus, they suggest. Also, H-SRT allows for precise treatment and a possible reduction in toxicity.

The authors note that this approach makes economic sense — in a couple of ways.

"Although the cost of re-irradiation is already a fraction of the cost of systemic maintenance therapy, examination of Medicare reimbursement rates for H-SRT demonstrated a cost savings of 20% (i.e., $4498.07 compared with $5705.47) with 10 treatments, compared with the 18 treatments of a typical fractionation schedule," they explain.

With these thoughts in mind, the investigators designed the study.

All the study participants were diagnosed with recurrence on the basis of radiographically identified tumor progression. Clinical judgment was used to define eligibility for H-SRT, the authors explain.

At Thomas Jefferson University, patients are generally eligible for treatment if the tumor volume is within a 10 × 10 cm field, the Karnofsky performance score (KPS) is 60 or higher, and the patients are able to lie flat for treatment planning and delivery.

The 147 patients had either grade 3 astrocytoma (n = 42; 29%) or glioblastoma multiforme (n = 105; 71%), and all had clinical and radiographic evidence of tumor progression.

All patients were followed with magnetic resonance imaging scans, which were obtained 6 to 8 weeks after H-SRT and at 3-month intervals from then on.

All patients had received initial postoperative conformal fractionated radiotherapy to a median dose of 60 Gy in daily 2 Gy fractions.

In all, 110 patients received chemotherapy at the time of initial diagnosis, and 48 received chemotherapy at recurrence with H-SRT.

All patients underwent neurosurgical intervention at initial diagnosis, and 84 patients (60%) had resection at recurrence before salvage H-SRT.

"Overall, the groups with resection plus H-SRT and with H-SRT alone were balanced with respect to initial treatment regimen, time to progression, dose of re-irradiation, and presence of multiple lesions," summarize the authors.

Study Results

Using H-SRT in 3.5 Gy fractions to 35.0 Gy, the investigators reported no grade 3 toxicities or reoperation secondary to toxicity in the patients. This provides "additional support that this dose and fraction size is well tolerated," they write.

There was also no survival benefit when chemotherapy was added to the radiation, report the authors.

"Although it was not a randomized trial, our study did not demonstrate a survival advantage in combining chemotherapy with H-SRT at recurrence compared with patients who received H-SRT alone," they write.

Despite the variability of the participants, their initial treatments, and salvage therapies, the authors observe that "all groups of patients benefited similarly from H-SRT, achieving a uniform" median survival time of 11 months.

A RADICAL cancer treatment pioneered in Melbourne is being hailed a global lifesaver.

A Victorian woman who had incurable liver cancer has been treated and her specialist is convinced she is cured.

Another patient, told he had only months to live in November, will celebrate his birthday on Tuesday with the news that his liver tumours have shrunk significantly.

Gordon Howgate, 58, said he was feeling pretty good and "I am optimistic that soon all the tumours will be gone".

More than 100 Victorians with inoperable liver cancer have been treated successfully with the revolutionary therapy known as SIRT (selective internal radiation therapy). They are part of a Melbourne-led international human trial of SIRT, used in conjunction with the chemotherapy drug sorafenib.

An Australian-owned discovery, SIRT is a one-off treatment where tiny radioactive beads, about one-third the width of a human hair, are injected into an artery near the groin. There, the beads lodge in the liver and release a radiation dose over a number of days to shrink tumours.

Associate Prof Peter Gibbs is a medical oncologist from the Royal Melbourne Hospital who has pioneered the therapy that was discovered by surgeon Bruce Gray. Seven years ago Prof Gibbs first used the SIRT on a patient, a lecturer at Melbourne University, with incurable liver cancer.

"Her tumours slowly disappeared and she remains tumour free. I am convinced that she is cured," he said.

She is one of more than 100 Victorians with inoperable liver cancer treated successfully. Most had a secondary cancer from bowel, breast or other organs spread to the liver.

Though primary liver cancer is rare in Australia, it is one of the most common and deadliest cancers worldwide.

Usually caused by exposure to hepatitis B and C, lifestyle is also a potential factor with excessive alcohol consumption a major risk.

In the past decade there has been a 50 per cent increase in this cancer in Australia, with men more at risk. Until now there was no potential cure because most patients could not be operated on or tolerate chemotherapy.

Mr Howgate was diagnosed with bowel cancer last year that had spread extensively to his liver.

"I asked how long I had without treatment and was told three to six months," Mr Howgate said.

The Melton father is one of our oldest surviving kidney transplant patients.

Following his treatment in November and six months of chemo, recent scans reveal his liver cancer has shrunk significantly and continues to.

Prof Gibbs said in about 5 per cent of patients tumours disappeared and in most others it was prolonging lives.

(NaturalNews) A Missouri hospital has admitted that it subjected 76 patients to 50 percent overdoses of brain radiation because a medical device had been programmed improperly.

According to the administration of CoxHealth in Springfield, a stereotactic radiation therapy device was programmed improperly after the hospital first installed it in 2004, even with an employee of the manufacturer supervising. For the next five years, every patient using the machine was exposed to 50 percent overdose. The error was only discovered in September 2009, when a new technician was being trained. A similar case occurred at the Moffitt Cancer Center in Tampa, Fla., in 2004 and 2005.

The hospital has suspended its stereotactic imaging program indefinitely for a full program audit.

The news comes on the heels of a scandal in which hundreds of patients in California and Alabama received as much as eight times the intended dose of chest radiation, and a new FDA initiative to reduce excess radiation from CT scans, nuclear medicine studies and fluoroscopies.

Robert H. Bezanson, president of CoxHealth, issued an open letter calling on the FDA to go farther.

"The initiative should be broadened to include regulation of medical radiation therapy as well," he wrote. "We have also learned that the incident here at CoxHealth is, unfortunately, not an isolated occurrence. Rather, similar instances of medical overradiation have occurred at other hospitals throughout the country. Without increased regulation and oversight, these instances of medical overradiation will likely continue."

Stereotactic radiation therapy employs ultra-high radiation doses to treat very small, localized brain tumors. Because the radiation dose is so high, only one treatment is normally needed.

Health professionals and the radiation imaging industry have increasingly raised concerns that many radiation devices are not calibrated or used properly, exposing patients to dangerous, higher-than-necessary doses. In many ways, they say, advances in imaging technology have outpaced doctors' ability to keep up.

PURPOSE: Salvage options for recurrent high-grade gliomas (HGGs) are limited by cumulative toxicity and limited efficacy despite advances in chemotherapeutic and radiotherapeutic techniques. Previous studies have reported encouraging survival results and favorable toxicity with fractionated stereotactic radiotherapy, and small studies have shown similar benefit using a shortened course of hypofractionated stereotactic radiation therapy (H-SRT). We sought to determine the efficacy and toxicity profile of H-SRT alone or in addition to repeat craniotomy or concomitant chemotherapy.

PATIENTS AND METHODS: Between 1994 and 2008, 147 patients with recurrent HGG were treated with H-SRT (median dose, 35 Gy in 3.5-Gy fractions). Cox regression models were used to analyze survival outcomes. Variables included age, surgery before H-SRT, time to first recurrence, reirradiation dose, inclusion of chemotherapy with H-SRT, and gross tumor volume (GTV).

RESULTS: Younger age (P = .001), smaller GTV (P = .025), and shorter time between diagnosis and recurrence (P = .034) were associated with improvement in survival from H-SRT. Doses of radiation > or = 35 Gy approached significance (P = .07). There was no significant benefit of surgical resection or chemotherapy in this population when analysis was controlled for other prognostic factors.

CONCLUSION: H-SRT was well tolerated and resulted in a median survival time of 11 months after H-SRT, independent of re-operation or concomitant chemotherapy. Patients who experienced recurrence within 6 months after initial treatment had an excellent response and should not be disqualified from H-SRT. This is the largest series to examine the efficacy and tolerability of H-SRT in recurrent HGG.

A multi-institution phase II study of poly-ICLC and radiotherapy with concurrent and adjuvant temozolomide in adults with newly diagnosed glioblastoma

Abstract

The objectives of this study were to determine the safety and efficacy of polyinosinic-polycytidylic acid stabilized with poly-l-lysine and carboxymethylcellulose (poly-ICLC) when added to radiation and temozolomide (TMZ) in adults with newly diagnosed glioblastoma (GB). Patients received external beam radiation with concurrent TMZ (75 mg/m(2)/day) followed by adjuvant TMZ (150-200 mg/m(2)/day for 5 consecutive days once every 9 weeks) and intramuscular poly-ICLC (20 mg/kg/dose given 3x per week for weeks 2-8). An adjuvant cycle was operationally defined as 9 weeks and patients continued adjuvant therapy until toxicity or disease progression. Ninety-seven patients were enrolled (60 men) with a median age of 56 years (range 21-85) and Karnofsky performance status of 90% (range 60%-100%). Fourteen patients did not start adjuvant treatment. Common treatment-related Grade 3-4 toxicities included neutropenia (20.6%), leukopenia (16.5%), thrombocytopenia (9%), and rash (1%). The entire cohort had a median survival of 17.2 months (95% CI: 15.5-19.3 months) with survival at 12, 18, and 24 months of 73.2%, 47.4%, and 29.9%. For subjects 18-70 years old, median overall survival was 18.3 months (95% CI: 15.9-19.8 months), as compared with 14.6 (95% CI: 13.2-16.8) reported by the EORTC 26981/22981 trial. These results demonstrate that poly-ICLC can be added to standard radiation and TMZ in patients with newly diagnosed GB without additional significant toxicities. Survival data at 12 and 18 months suggest that this may improve the efficacy of chemoradiation and adjuvant TMZ in this patient population.

Australian-led research published in the Journal of Clinical Oncology has found getting radiotherapy just right does more to save cancer patients' lives than receiving more drugs.

Lead researcher Professor Lester Peters, from the Peter McCallum Cancer Centre in Melbourne, says receiving additional drug treatments is not always the best approach.

"The history of cancer research is that as you add each new drug or biological you gain an incremental improvement usually of a few per cent," he told ABC Radio's AM.

"What we've shown for the first time, and very dramatically, is that unless the platform treatment and the new incremental improvements is done in a competent way it's all a waste of time.

"It's no good having fancy icing on the cake if the cake is not baked properly."

The basic finding of the paper is that radiotherapy is more successful when administered according to protocol.

"It is intuitive but strangely enough it's never been documented quantitatively before and the magnitude of the effect is what is astounding," Professor Peters said.

The results come from a large international trial designed to investigate a new drug that would improve survival of patients with advanced head and neck cancer when added to radiotherapy.

The study found the quality of radiotherapy was much more significant.

"The difference in survival between patients who got acceptable or unacceptable radiotherapy was 20 per cent at two years," Professor Peters said.

"It was 70 per cent survival when those who got good radiotherapy and only 50 per cent in those who got unsatisfactory radiotherapy."

He says head and neck cancer patients had a higher probability of receiving sub-standard radiotherapy in smaller centres that only treated a few patients with the condition.

"Several Australian centres participated in this trial but they were all major centres and so the non-compliance rate was fairly low in Australia," Professor Peters said.

"However, the logical extrapolation of our results in the context of Australia is that as more and more regional cancer centres are opened up there are certain types of complex cancers that are probably still best treated in major centres.

"The difficulty is to reconcile the convenience of treatment in the regions with the impossibility with maintain sub-specialty expertise in every small facility."

ScienceDaily (July 22, 2010) — A new approach to processing X-ray data could lower by a factor of ten or more the amount of radiation patients receive during cone beam CT scans, report researchers from the University of California, San Diego.

Cone beam CT plays an essential role in image-guided radiation therapy (IGRT), a state-of-the-art cancer treatment. IGRT uses repeated scans during a course of radiation therapy to precisely target tumors and minimize radiation damage in surrounding tissue. Though IGRT has improved outcomes, the large cumulative radiation dose from the repeated scans has raised concerns among physicians and patients.

Reducing the total number of X-ray projections and the mAs level per projection (by tuning down the X-ray generator pulse rate, pulse duration and/or current) during a CT scan can help minimize patient's exposure to radiation, but the change results in noisy, mathematically incomplete data that takes hours to process using the current iterative reconstruction approaches. Because CBCT is mainly used for treatment setup while patients are in the treatment position, fast reconstruction is a requirement, explains lead author Xun Jia, a UCSD postdoctoral fellow.

The research is being presented at the 52nd Annual Meeting of the American Association of Physicists in Medicine (AAPM) in Philadelphia.

Based on recent advances in the field of compressed sensing, Jia and his colleagues developed an innovative CT reconstruction algorithm for graphic processing unit (GPU) platforms. The GPU processes data in parallel -- increasing computational efficiency and making it possible to reconstruct a cone beam CT scan in about two minutes. (Modern GPU cards were originally designed to power 3D computer graphics, especially for video games.)

With only 20 to 40 total number of X-ray projections and 0.1 mAs per projection, the team achieved images clear enough for image-guided radiation therapy. The reconstruction time ranged from 77 to 130 seconds on an NVIDIA Tesla C1060 GPU card, depending on the number of projections -- an estimated 100 times faster than similar iterative reconstruction approaches, says Jia.

Compared to the currently widely used scanning protocol of about 360 projections with 0.4 mAs per projection, Jia says the new processing method resulted in 36 to 72 times less radiation exposure for patients.

"With our technique, we can reconstruct cone beam CT images with only a few projections -- 40 in most cases -- and lower mAs levels," he says. "This considerably lowered the radiation dose."

The reconstruction algorithm is part of the UCSD group's effort to develop a series of GPU-based low dose technologies for CT scans.

"In my mind, the most interesting and compelling possibilities of this technique are beyond cancer radiotherapy," says Steve Jiang, senior author of the study and a UCSD associate professor of radiation oncology.

"CT dose has become a major concern of medical community. For each year's use of today's scanning technology, the resulting cancers could cause about 14,500 deaths.

"Our work, when extended from cancer radiotherapy to general diagnostic imaging, may provide a unique solution to solve this problem by reducing the CT dose per scan by a factor of 10 or more," says Jiang.

ScienceDaily (July 22, 2010) — Patients with deadly glioblastomas who received high doses of radiation that hit a portion of the brain that harbors neural stem cells had double the progression-free survival time as patients who had lower doses or no radiation targeting the area, a study from the Radiation Oncology Department at UCLA's Jonsson Comprehensive Cancer Center has found.

Patients who underwent high doses of radiation that hit the specific neural stem cell site, known as the stem cell niche, experienced 15 months of progression-free survival, while patients receiving lower or no doses to this region experienced 7.2 months of progression-free survival, said Dr. Frank Pajonk, an associate professor of radiation oncology, a cancer center researcher and senior author of the study.

Pajonk said the study, published in the early online edition of the journal BMC Cancer, could result in changes in the way radiation therapy is given to patients with these deadly brain cancers.

"Our study found that if you irradiated a part of the brain that was not necessarily part of the tumor the patients did better," Pajonk said. "We have been struggling for years to come up with new combinations of drugs and targeted therapies that would improve survival for patients with glioblastoma. It may be that by re-shaping our radiation techniques we can extend survival for these patients."

The retrospective study focused on the cases of 55 adult patients with grade 3 or grade 4 glioblastomas who received radiation at UCLA between February 2003 and May 2009. Pajonk said a prospective study is needed to confirm the results.

There is some evidence that many if not all cancers may spring from stem cells or progenitor cells that normally repair damage to the body, but that somehow become mutated and transform into cancer. In this case, Pajonk said the neural stem cell niche, called the periventricular region of the brain, may also be harboring stem cells that have transformed into brain cancer stem cells. However, the niche serves as a sort of safe harbor for the cancer stem cells, keeping them away from the site of the tumor but able to re-grow it once it's removed and the malignant areas of the brain have been treated.

Pajonk theorizes that the brain cancer stem cells in the patients whose niches were irradiated with higher doses may have been damaged or eliminated, giving these patients more time before their cancer recurred.

Glioblastomas are the deadliest form of brain cancer. Surgery, chemotherapy and radiation are not usually effective and life expectancy is about 12 to 18 months. New and more effective treatments are needed to help this patient population, Pajonk said.

The radiation therapy could damage neural stem cells as well as the cancer stem cells, Pajonk said, but those may be replaceable at some future date using induced pluripotent stem cells made from the patient's own cells. The induced pluripotent stem cells, which like embryonic stem cells can make every cell in the body, could be induced into becoming neural stem cells to replace those damaged or eradicated by the radiation to the niche.

When Alain Reyes’s hair suddenly fell out in a freakish band circling his head, he was not the only one worried about his health. His co-workers at a shipping company avoided him, and his boss sent him home, fearing he had a contagious disease.

Only later would Mr. Reyes learn what had caused him so much physical and emotional grief: he had received a radiation overdose during a test for a stroke at a hospital in Glendale, Calif.

Other patients getting the procedure, called a CT brain perfusion scan, were being overdosed, too — 37 of them just up the freeway at Providence Saint Joseph Medical Center in Burbank, 269 more at the renowned Cedars-Sinai Medical Center in Los Angeles and dozens more at a hospital in Huntsville, Ala.

The overdoses, which began to emerge late last summer, set off an investigation by the Food and Drug Administration into why patients tested with this complex yet lightly regulated technology were bombarded with excessive radiation. After 10 months, the agency has yet to provide a final report on what it found.

But an examination by The New York Times has found that radiation overdoses were larger and more widespread than previously known, that patients have reported symptoms considerably more serious than losing their hair, and that experts say they may face long-term risks of cancer and brain damage.

The review also offers insight into the way many of the overdoses occurred. While in some cases technicians did not know how to properly administer the test, interviews with hospital officials and a review of public records raise new questions about the role of manufacturers, including how well they design their software and equipment and train those who use them.

The Times found the biggest overdoses at Huntsville Hospital — up to 13 times the amount of radiation generally used in the test.

Officials there said they intentionally used high levels of radiation to get clearer images, according to an inquiry by the company that supplied the scanners, GE Healthcare.

Experts say that is unjustified and potentially dangerous.

“It is absolutely shocking and mind-boggling that this facility would say the doses are acceptable,” said Dr. Rebecca Smith-Bindman, a radiology professor who has testified before Congress about the need for more controls over CT scans. Yet because the hospital said no mistakes were made, regulatory agencies did not investigate.

The F.D.A. was unaware of the magnitude of those overdoses until The Times brought them to the agency’s attention. Now, the agency is considering extending its investigation, according to Dr. Alberto Gutierrez, an F.D.A. official who oversees diagnostic devices.

Patients who received overdoses in Huntsville say that in addition to hair loss, they experienced headaches, memory loss and confusion. But at such high doses, experts say, patients are also at higher risk of brain damage and cancer.

A spokesman for Huntsville Hospital, which now acknowledges that some patients received “elevated” radiation, said officials there would not comment.

Growing Number of Cases

So far, the number of patients nationwide who got higher-than-expected radiation doses exceeds 400 at eight hospitals, six in California alone, according to figures supplied by hospitals, regulators and lawyers representing overdosed patients. A health official in California who played a leading role in uncovering the cases predicts that many more will be found as states intensify their search.

“I cannot believe that this is not occurring in the rest of the country,” said Kathleen Kaufman, head of radiation management for the Los Angeles County Department of Public Health. “That’s why we are so keen on the rest of the states to go look at this.”

The Food and Drug Administration acknowledges, too, that the number does not capture all the overdoses.

The cases come at a time when Americans are receiving more medical radiation than ever before, a result of rapid technological advancements that improve diagnosis but can also do harm when safeguards and oversight fail to keep pace.

Even when done properly, CT brain perfusion scans deliver a large dose of radiation — the equivalent of about 200 X-rays of the skull. But there are no hard standards for how much radiation is too much. The overdoses highlight how little some in the medical profession understand about the operation of these scanning devices and the nature of radiation injuries, as well as the loose requirements for reporting accidents when they are detected.

For a year or more, doctors and hospitals failed to detect the overdoses even though patients continued to report distinctive patterns of hair loss that matched where they had been radiated. After the Food and Drug Administration issued a nationwide alert asking hospitals to check their radiation output on these tests, a few hospitals continued to overdose patients for weeks and in some cases months afterward, according to records and interviews.

ScienceDaily (Aug. 11, 2010) — Currently, new treatment facilities for radiation therapy with ions are built all over the world. These particles destroy cancer cells and have a better ability to spare the surrounding healthy tissue than other techniques. Today, accelerated hydrogen and carbon ions are mainly used to treat inoperable tumors in organs like the brain and bone marrow, which are sensitive to radiation therapy. A new technology for this kind of treatment is developed by researchers of the OncoRay center in Dresden and of the research center Forschungszentrum Dresden-Rossendorf (FZD): in their concept the ion beams are accelerated by a compactlaser, and not in 'normal' accelerators.

They published their first results of cell irradiations using ions in the New Journal of Physics.

Traditional proton and ion accelerators are large and expensive, which is why the new therapy making use of accelerated proton and ion beams can only be applied in a few clinics like the Heidelberg Ion-Beam Therapy Center (HIT). Yet there is a big world-wide interest in compact and flexible facilities for proton and ion acceleration for therapy, as experts expect the proof of the advantages of proton and ion therapy for an increasing group of different cancer diseases in the future leading to widespread clinical application. The Dresden OncoRay center, which is carried by the research center Forschungszentrum Dresden-Rossendorf (FZD), University Hospital Dresden and TU Dresden, now achieved an important step towards compact radiation facilities for cancer treatment.

The high-power laser DRACO at the FZD generates protons, accelerating them on a very short scale of less than ten micrometers (which is about one tenth of the thickness of a single human hair). For their current results, the team of researchers led by Dr. Ulrich Schramm (FZD) and Dr. Jörg Pawelke (OncoRay) irradiated cancer cells with protons, i.e. hydrogen atoms where the electron is missing. The scientists are also investigating the impact of radiation on cells under controlled conditions, for which they developed a special device enabling them to precisely measure the dose of the irradiated cells. The dose of the irradiations at the FZD ranged between 1.5 and 4 gray -- an area particularly relevant for clinical application of proton beams. What is more, the energy of the laser accelerated ion beam is high enough for the first time for the beam to be able to penetrate into tissue, but also into other materials, enabling exact dose detection. Up to 20 mega electron volts were achieved in the experiments.

60 percent of cancer patients receive traditional radiation therapy

The advantage of accelerated ion beams is that they have their highest impact in the tumor and, thus, have a better ability to spare healthy tissue. Today, more than 60 percent of cancer patients undergo radiation therapy. While, in traditional therapy, a considerable part of the energy of photon beams generated in modern clinical linear accelerators is emitted on their way through healthy tissue, ion beams can be stopped right in the tumor with utmost precision, where their damaging impact is released on all tumor cells. This new method was successfully tested in the heavy ion therapy project at GSI, Darmstadt, among other things. About 400 patients were treated and about 70 percent of them were cured. FZD scientists collaborated in this project and are also significantly involved in the Heidelberg HIT center.

New kinds of radiation to combat cancer

There is still a lot of basic research to be done until the first clinical applications of high-power lasers. Scientists from Dresden are strongly involved in this and are likely to make essential contributions to the world-wide run for new applications, drawing on the close collaborations of medical scientists, physicists, biologists and mathematicians in Dresden. The OncoRay center forms a unique cluster for radiation research in oncology in Dresden and has made a name for itself on an international level. OncoRay scientists at the university hospital, FZD and TU Dresden are focused on translational research, which means that results from basic research are to be transferred to clinical applications as soon as possible. The first compact irradiation facility applying laser technology could be put up in hospitals in ten to fifteen years.

The next step towards clinical application is to carry out detailed studies comparing the impact of laser accelerated ion beams with radiation traditionally used in cancer therapy. In addition, scientists from Dresden and of the Friedrich-Schiller-Universität and the Fraunhofer Institute in Jena are accomplising studies in order to increase the energy of the radiation, in the framework of the "onCOOPtics" project. Researchers also aim at developing a prototype for laser based radiation therapy to be installed at a new joint center for radiation therapy in oncology in Dresden.

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